Episode Transcript:

Dr. Frank Maddux: Human acellular vessels or bioengineered blood conduits, which have shown great promise in clinical trials for vascular applications, including arterial venous access for hemodialysis, peripheral arterial disease, and trauma repair. Today's guest, Dr. Laura Nicholson, founder and CEO of Humacyte, is here to discuss this promising technology and its recent deployment as humanitarian aid for repairing vascular trauma in the Ukraine.

Welcome, Laura. Thanks for joining me.

Dr. Laura Niklason: Thank you for having me, Frank. It's great to be here.

Dr. Frank Maddux: Describe the HAV a little bit and tell people about what it is in case they haven't already heard.

Dr. Laura Niklason: The human acellular vessel, or HAV is a bio engineered blood vessel. It's an artery that is grown from human cells in our manufacturing suite. I like to say that these arteries are grown from scratch. We're starting with vascular cells and coaxing these cells to form a brand-new artery in a bioreactor. This process is based on about 25 or 30 years’ worth of science that's been done at Humacyte but also at several universities in the U.S.

What's really exciting about the HAV is not just that we can grow a new human artery from cells, and we can do this at commercial scale. But what's really important for patients is that this artery, after we complete growing the artery is then decellularized. And what that means is that we grow a new human tissue, but then we rinse the cells out of the tissue at the end of the culture process.

This gives us an engineered blood vessel that has no cells, and therefore, really can't be rejected by any human recipient. This also means that our engineered tissues can be stored on the shelf for up to a year and a half in the hospital. So, we've implanted the human acellular vessel in patients with kidney failure who need access for dialysis, but also in patients with peripheral arterial disease and patients suffering vascular trauma. In fact, we've implanted more than 500 patients across these different indications.

Dr. Frank Maddux: We've talked before about the uses in dialysis to and the population of patients that might benefit from an HAV as opposed to a traditional PTFE graft. If you could just quickly comment on where you are in the current profile of looking at the use of the HAV in dialysis patients.

Dr. Laura Niklason: We have two phase-three trials that we've undertaken. One is in long term follow up and another trial is still enrolling. This is a trial that's comparing the HAV to arterioveinous fistula in about 25 sites in the US. What our first phase-three trials showed was that the HAV was durable and was reliably usable for for dialysis after a period of 4 to 8 weeks, which may provide an advantage over autologous fistulas, which in some patients can take many months to mature.

We also saw in our first trial that the failure rate due to infection, the rate of conduit infection of the HAV, was much lower, significantly lower than it was for PTFE grafts. In the current trial, which is a phase-three trial that we're still enrolling, although we're almost done, we're looking at the usability for dialysis of the HAV at six and 12 months as compared to arterioveinous fistula.

We anticipate that because the HAV is reliably usable for dialysis a month or two after implantation and it doesn't have to mature or dilate. This means that, within the first year, we would anticipate that the usability of the HAV will be higher than it is for fistula. In addition, because the infection rate of the HAV is so low, this may provide patients with a high quality, durable access that resists infection and can allow these patients to have their catheters removed earlier and save them morbidity associated with prolonged catheter exposure.

Dr. Frank Maddux: There are other uses for the HAVs, and I'm wondering if you might just tell us a little bit about other ways in which vascular repair or vascular creation and uses outside of sort of the end-stage kidney disease population. What you're looking at there?

Dr. Laura Niklason: We have two phase-two trials, which are now in long term follow up, where we've treated patients with severe peripheral arterial disease. We did one trial in Europe and another in the U.S. And In both cases, we're looking at patients with severe limb ischemia. And In the U.S. trial, we were looking at critical limb ischemia. So, patients with rest pain or patients who were already experiencing tissue loss.

What we've seen is that the HAV in these patients has had good function, has shown durability. In fact, we have follow up now going out to six years and longer, showing that the HAV is durable and doesn't dilate and also doesn't become narrowed over time. We've also seen a similar outstanding infection profile. So, we've had no instances of HAV infection in any of our peripheral arterial disease patients.

This resistance to infection, combined with the durability, has really contributed to the U.S. Defense Department designating the the HAV as a priority product back in 2018. The reason for this is that the Defense Department is interested in, at some point, having the HAV as a tool in their toolbox to treat wounded war fighters. Since soldiers oftentimes have complex wounds that are contaminated and dirty and having a vascular conduit that's immediately available and resists infection could really be a game changer for wounded war fighters.

Dr. Frank Maddux: I'm aware of the use of the HAV in the conflict in Ukraine. Can you tell us a little bit about how that came about and what the process of getting authorizations to use these have been?

Dr. Laura Niklason: Yes, this has been a very interesting journey for our company, Frank. It's been wonderful to be able to help in a small way with this ongoing conflict. So as your guests may remember, the Russian Federation invaded Ukraine on February 24th of this year. In March, Humacyte began receiving a number of requests from surgeons who were in frontline hospitals in Ukraine and who were treating war wounded, asking for access to the HAV to help them treat some of their injured patients.

We then reached out to the FDA office, of their international office, to gain clearance to allow us to ship the HAV over to Ukraine. Because, again, the HAV is not yet approved in the U.S. or elsewhere. So, the international office of the FDA was actually very supportive, and they granted us permission to do this very quickly. We then worked with the Ukrainian Ministry of Health and got their clearance to bring the product into the country.

In fact, they were also very helpful and have even supported our efforts to distribute the product from a central depot to five frontline hospitals in Ukraine. This whole process between the regulatory clearances and then shipping the product actually took several months. But we did get HAVs to frontline hospitals early in June of this year.

Dr. Frank Maddux: Tell us a little bit about how they've been used in patients at this point.

Dr. Laura Niklason: Well, again, this is a humanitarian effort thus far. So, the vessels have been sent in not as part of a clinical trial, but as part of a humanitarian effort. All of the information that we get back from treating surgeons is based on their excitement and their willingness to share outcomes of the product with their patients.

We've currently treated five patients at three different hospitals in Ukraine. These patients have all suffered traumatic injury with several gunshot wounds and several shrapnel injuries from mine blasts. Some of these wounds are discrete and some of these wounds are devastating. We used an HAV to to salvage the limb of one patient who was really badly injured by a mine blast in his in essentially all four limbs as well as his torso recently.

What we have seen so far from the information that we have, is that for each of these patients, the HAV has functioned well and has remained patent. And In fact, our surgeons tell us that that we've already saved a number of limbs in people who are injured in this conflict. So we're very grateful to be able to work with the Ukrainian surgeons and help these patients.

Dr. Frank Maddux: The humanitarian effort is almost one of the things that this was designed for and that these are essentially vessels, human vessels off the shelf. It's both interesting scientifically and medically to see how these are being used. But also as a humanitarian effort, it certainly is something to try to help people that are in such difficult straits right now.

Dr. Laura Niklason: I certainly agree. And I think the findings that we're seeing in Ukraine really vindicate the decision of the Defense Department to make this a priority product several years ago. What the Defense Department was hoping to see, for better or for worse, is unfolding in Ukraine right now. So, I think that it just shows the utility of the product.

It also shows that we were able to train surgeons and caregivers remotely. We train surgeons over Zoom on the implantation of this product. And that was very effective.

Dr. Frank Maddux: Before we end, any other final comments on just this state of things at Humacyte, as we begin to work our way out of the relatively difficult few years of pandemic. It's it's been an exciting few years for Humacyte I know.

Dr. Laura Niklason: Certainly Humacyte has been affected by the pandemic as everyone has. I would say probably one of the biggest effects of the pandemic for us has been both slowing our phase three trial enrollment, because anything that wasn't a COVID trial was seriously slowed down during the pandemic. But in addition, Humacyte’s engineered vessel, even though we talk about it as a graft or a tissue, is actually regulated as a biologic.

So we're regulated by the Center for Biologics at the FDA, which, as we all know, has been a little bit distracted with COVID vaccines and COVID therapies in recent years. So Humacyte has essentially had to walk uphill a little bit and and try to get our trials enrolled, but also try to work with the limited bandwidth that the FDA has had in the last few years.

But that being said, we're making progress. The partnership with Fresenius has been fabulous for us. And In fact, we're doing a research project right now with Frenova to really look at patients in the U.S. and Europe who have difficulties with their vascular access to really pinpoint the patients who might most benefit from an HAV once it's approved and once we're on the market.

Dr. Frank Maddux: Thanks, Laura. Any final comments and otherwise? I really appreciate the time today to talk to us about both the HAVs Humacyte and how you were able to utilize these vessels in such an important way in the Ukraine.

Dr. Laura Niklason: I want to thank you for for making the time for this. You know, I do think that regenerative medicine is becoming a reality. You know, one of the taglines we have at Humacyte is that this used to be science fiction, but now it's science fact. And I'm really looking forward to the next few years and seeing how we can help more patients.

Dr. Frank Maddux: I've been here today with Dr. Laura Nicholson, founder and CEO of Humacyte, talking about the use of the HAV in the Ukraine and how the company continues, despite pandemic and many challenges, to continue to move forward in their program of bringing these tissue engineered vessels to the market. Laura, thanks so much for being with me today.

Dr. Laura Niklason: Thank you.